Tyrone Cannon

Yale University | YU · Department of Psychology

Experimental cognitive tests are designed to measure particular cognitive domains, although evidence supporting test validity is often limited. The Consortium for Neuropsychiatric Phenomics test battery administered 23 experimental and traditional neuropsychological tests to a large sample of community volunteers ( n = 1,059) and patients with psyc...

Background Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical,...

Background and Hypothesis Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator. St...

Cognitive models of delusions emphasize the role of bias against disconfirmatory evidence (BADE) in maintaining false beliefs, but sources of this tendency remain elusive. While impaired information integration could be an explanation for this tendency, the lack of information seeking motive could also result in disregard for new evidence once a (f...

Importance Schizophrenia and bipolar disorder are highly heritable psychiatric disorders with strong genetic and phenotypic overlap. Twin and molecular methods can be leveraged to predict the shared genetic liability to these disorders. Objective To investigate whether twin concordance for psychosis depends on the level of polygenic risk score (PR...

Introduction The clinical high-risk state for psychosis (CHR) is associated with alterations in grey matter volume (GMV) in various regions such as the hippocampus (Vissink et al. BP:GOS 2022; 2(2) 147-152). Within the scope of the North American Prodrome Longitudinal Study (NAPLS-2; Cannon et al. AM J Psychiatry 2016; 173(10), 980-988), a publicly...

Introduction Schizophrenia is a mental health condition that severely impacts well-being. Cognitive impairment is among its core features, often presenting well before the onset of psychosis, underscoring a critical need to study it in the psychosis proneness stage, to maximize the benefits of interventions and to improve clinical outcomes. However...

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectu...

Monozygotic (MZ) twins are often thought to have identical genomes, but recent work has shown that early post-zygotic events can result in a spectrum of DNA variants that are different between MZ twins. Such variants may explain phenotypic discordance and contribute to disease etiology. Here we performed whole genome sequencing in 17 pairs of MZ tw...

Aims: The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. Methods: The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high r...

Background and Hypothesis The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric str...

Background and Hypothesis Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the...

Aim There is limited research on the effects of sociodemographic and socioeconomic factors on treatment outcomes in youth at clinical high risk for psychosis (CHRp). This study examined sociodemographic factors that may affect functional outcomes within this population. Specifically, we investigated the influence of race/ethnicity (dichotomized as...

Background: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) have subthreshold psychosis symptoms without known genetic risk factors. Whether common neural substrates underlie these distinct high-risk populations...

The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium’s transdiagnostic dimensional model of psychopathology has considerable support; however, this model has been underresearched in individuals at clinical high risk for psychosis (CHR-P), a population that may advance the model. CHR-P individuals not only have attenuated psychotic sympto...

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of m...

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of...

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accu...

This review describes the Hierarchical Taxonomy of Psychopathology (HiTOP) model of psychosis-related psychopathology, the psychosis superspectrum. The HiTOP psychosis superspectrum was developed to address shortcomings of traditional diagnoses for psychotic disorders and related conditions including low reliability, arbitrary boundaries between ps...

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Objective Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period...

Status threat (i.e., concern that one’s dominant social group will be undermined by outsiders) is a significant factor in current United States politics. While demographic factors such as race (e.g., Whiteness) and political affiliation (e.g., conservatism) tend to be associated with heightened levels of status threat, its psychological facets have...

Schizophrenia is characterized by memory impairments, yet the relationships between its distinct symptom clusters (i.e., positive, negative, disorganized) and specific aspects of memory dysfunction remain poorly characterized. In the present study, we compiled a large analog sample (N = 795) to test whether positive symptoms, versus negative and di...

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS)...

Importance: The protective ethnic density effect hypothesis, which suggests that minoritized individuals who grow up in neighborhoods with a high proportion of ethnoracial minoritized groups are protected from the effects of perceived discrimination, has not been examined among individuals at clinical high risk of psychosis (CHR-P). This level of...

Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy pa...

Importance: Leveraging the dynamic nature of clinical variables in the clinical high risk for psychosis (CHR-P) population has the potential to significantly improve the performance of outcome prediction models. Objective: To improve performance of prediction models and elucidate dynamic clinical profiles using joint modeling to predict conversi...

An ethnoracial minority density (EMD) effect in studies of psychotic spectrum disorders has been observed, whereby the risk of psychosis in ethnoracial minority group individuals is inversely related to the proportion of minorities in their area of residence. The authors investigated the relationships among area-level EMD during childhood, cortical...

Background and hypothesis: Although studies have identified social fragmentation as an important risk factor for schizophrenia and other psychotic disorders, it is unknown whether it may impact social functioning. This study investigates whether social fragmentation during childhood predicts maladaptation to school as well as social functioning du...

Novelty detection is critical to the effective employment of memory-guided behavior. While recent work has found impaired novelty detection in subclinical paranoia, other studies show different patterns. Here, we tested the hypothesis that those higher in paranoia receive less benefit from novelty in their immediate environment when making subseque...

Background and Hypothesis Negative symptom trajectory in clinical high risk for psychosis (CHR) is ill-defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonl...

Cognitive inflexibility has been linked to difficulties in revising paranoid beliefs, whereas cognitive flexibility may protect against the development and maintenance of paranoid beliefs by allowing for troubleshooting in light of available evidence. While less discussed in the context of paranoia research, better regulation of affective states ma...

Introduction Persistent negative symptoms (PNS) are described as continuing moderate negative symptoms. More severe negative symptoms have been associated with poor premorbid functioning in both chronic schizophrenia and first episode psychosis patients. Furthermore, youth at clinical high risk (CHR) for developing psychosis may also present with n...

Background Elevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased geneti...

Background and hypothesis: While individuals at clinical high-risk (CHR) for psychosis experience higher levels of discrimination than healthy controls, it is unclear how these experiences contribute to the etiology of attenuated positive symptoms. The present study examined the association of perceived discrimination with positive symptoms in a c...

Reduced hippocampal volume is an established brain morphological feature of psychiatric conditions. Hippocampal volume is associated with brain connectivity in humans and nonhuman animals, and altered connectivity is associated with risk for psychiatric illness. Associations between hippocampal volume and connectivity are poorly characterized in hu...

Introduction: Interpretation inflexibility has been implicated in a range of mental health problems, including depression, social anxiety, and paranoia. Inflexible interpretation of social situations may be particularly important as it can set the stage for problems in social functioning, a symptom cutting across all three groups of disorders. Meth...

Aim: Although violent behaviour has been studied in schizophrenia, violence risk has received little attention in individuals at clinical high risk for psychosis (CHR). This manuscript aims to report and discuss the overall results of the Structured Assessment for Violence Risk in Youth (SAVRY) from the NAPLS-3 project to explore the risk of viole...

Depression is associated with a bias toward negative interpretations of social situations and resistance to integrating evidence consistent with positive interpretations. These features could contribute to social isolation by generating negative expected value for future social interactions. The present study examined potential associations between...

Objective The Mini-SIPS, a condensed version of the Structured Interview for Psychosis-Risk Syndromes (SIPS), is intended to efficiently identify for clinicians the minimum information needed to support a DSM-5 Attenuated Psychosis Syndrome (APS) diagnosis. Methods The instrument and the DSM-5 criteria are accessible through the online training pr...

Background: Elevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genet...

Factors unrelated to skill are known to contribute to cognitive performance (Revelle, 1993). Specifically, cognitive effort during performance is required for success at many important tasks. Disengagement of effort during cognitive tasks may relate to impulsivity, as self-control may be needed to stay on task and persist in the face of difficulty...

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the...

Background The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cereb...

Paranoia is associated with difficulties in revising initial interpretations of social situations, a phenomenon that may help explain resistance of paranoid thoughts to modification by experience. But what leads individuals with paranoia to become suspicious of newly encountered others? The present study examined the relationship between paranoia a...

Purpose Migrant status is a known risk factor for psychosis, but the underlying causes of this vulnerability are poorly understood. Recently, studies have begun to explore whether migrant status predicts transition to psychosis in individuals at clinical high risk (CHR) for psychosis. Results, however, have been inconclusive. The present study asse...

Delusions can be conceptualized as beliefs that are both at odds with consensus reality and espoused with high conviction. While delusions represent a cardinal symptom of schizophrenia, delusion-like beliefs can be found in the general population. Do similar cognitive mechanisms support delusionality across this spectrum? If so, what are they? Here...

Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n=1138) comprised healthy part...

Background Choroid plexus (ChP) enlargement has been described in first-episode psychosis and psychosis spectrum disorders, but whether ChP enlargement occurs before disease onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to cli...

Background The auditory N100 is an event related potential (ERP) that is reduced in schizophrenia, but its status in individuals at clinical high risk for psychosis (CHR) and its ability to predict conversion to psychosis remains unclear. We examined whether N100 amplitudes are reduced in CHR subjects relative to healthy controls (HC), and this red...

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are highly heritable psychiatric disorders, as indicated by twin/pedigree and genomic studies. These two psychotic disorders also have considerable genetic overlap (rg=0.68). We investigated whether polygenic risk scores (PRS) could predict the concordance of co-twins for these psychotic di...

Introduction Area-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with decreased gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral ant...

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Hyperactivation of micro...

Cannabis use is more prevalent among youth at clinical high-risk (CHR) for psychosis than healthy controls (HC). There is mixed evidence as to whether cannabis use is associated with increased severity of attenuated psychotic symptoms (APS) or whether current cannabis use is associated with the transition to psychosis. This study aims to assess can...

Purpose Bullying is associated with a heightened risk for poor outcomes, including psychosis. This study aimed to replicate previous findings on bullying prevalence in clinical high-risk (CHR) individuals, to assess the longitudinal course of clinical and functional variables between bullied and non-bullied CHR and the association of bullying with...

Reductions in hippocampal volume (HV) have been associated with both prolonged exposure to stress and psychotic illness. This study sought to determine whether higher levels of neighborhood poverty would be associated with reduced HV among individuals at clinical high-risk for psychosis (CHR-P), and whether social engagement would moderate this ass...

Importance: Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P). Objective: To examin...